Cancer: Overview, Causes, Risk Factors, Treatment

Cancer: Overview, Causes, Risk Factors, Treatment

A 12-year study led by a team of University of Arizona Cancer Center researchers is bringing into question the safety and efficacy of selenium, a popular nutritional supplement touted to combat and reduce the risk of colorectal cancer.
The findings indicate the need for a significant change in practice, given that selenium supplements cannot be recommended for preventing colorectal cancer.
Selenium has been a popular nutritional supplement for decades, touted for its antioxidant properties and its role in stopping free radicals from damaging cells and DNA. Studies have shown a deficiency of this micronutrient to be associated with cancer risk.
However, a randomized clinical trial involving 1,824 participants from clinical centers in Arizona, Colorado, Texas and New York indicates that selenium supplements failed to prevent the development of colon polyps, but significantly increased the risk of developing type 2 diabetes in older individuals.

A new study indicates that adolescent females with acute leukemia have low rates of pregnancy screening prior to receiving chemotherapy that can cause birth defects. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society.
Although many chemotherapy drugs can cause birth defects, there are no standardized guidelines for pregnancy screening in adolescent female cancer patients and little is known about how often they are screened prior to treatment. To investigate, a team of researchers at the University of Pennsylvania Perelman School of Medicine and The Children’s Hospital of Philadelphia examined pregnancy screening patterns among adolescents with acute leukemia compared with adolescents with an emergency room (ER) visit who received computed tomography scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to known teratogenic risks of radiation.)
The analysis included acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and ER admissions in hospitals across the United States affiliated with the Pediatric Health Information System from 1999 to 2011.

Few effective treatments have been approved to treat ovarian cancer, the deadliest of all cancers affecting the female reproductive system. Now, new research from The Wistar Institute demonstrates how a drug already in clinical trials could be used to boost anti-tumor immunity and cause T-cells to target the cancer directly while minimizing side effects. The results were published in the journal Cell Reports.
There has been considerable interest in the programmed cell death-1 (PD-1) protein and its ligand (PD-L1) because the interaction between the two inhibits important T-cell activity aimed at stopping tumor growth. PD-L1 is expressed on the surface of both cancer cells and immune cells across many different cancer types. Antibody-based drugs that specifically halt this interaction have shown promising results, though patients have experienced immune-related side effects as a result.
“We wanted to explore anti-PD-L1 therapies specifically for ovarian cancer, but we also wanted to determine if other drugs that did not cause these negative anti-PD-L1 antibody-related side effects could be used to target this cancer-promoting pathway,” said Rugang Zhang, Ph.D., professor and co-program leader in the Gene Expression and Regulation program at The Wistar Institute and lead author of the study.

In a study appearing in the September 13 issue of JAMA, Jouke T. Annema, M.D., Ph.D., of the Academic Medical Center, Amsterdam, and colleagues examined five-year survival after endosonography vs mediastinoscopy for mediastinal nodal staging of lung cancer.
Accurate mediastinal nodal staging is crucial in the management of non-small cell lung cancer (NSCLC) because it directs therapy and has prognostic value. The Assessment of Surgical Staging vs Endosonographic Ultrasound in Lung Cancer (ASTER) trial compared mediastinoscopy (surgical staging) with an endosonographic staging strategy (which combined the use of endobronchial and transesophageal ultrasound followed by mediastinoscopy if negative). The endosonographic strategy was significantly more sensitive for diagnosing mediastinal nodal metastases than surgical staging (94 percent endosonographic strategy vs 79 percent surgical strategy). If mediastinal staging is improved, more patients should receive optimal treatment and might survive longer.
This analysis evaluated survival in ASTER. Of 241 patients with potentially resectable NSCLC, 123 were randomized to endosonographic staging and 118 to surgical staging in 4 tertiary referral centers. Survival data were obtained through patient records, death registers, or contact with general practitioners. Survival data at 5 years were obtained for 237 of 241 patients. The prevalence of mediastinal nodal metastases was 54 percent in the endosonographic strategy group and 44 percent in the surgical strategy group. Survival at 5 years was 35 percent for the endosonographic strategy vs 35 percent for the surgical strategy. The estimated median survival was 31 months for the endosonographic strategy vs 33 months for the surgical strategy.

A multi-institutional academic and industry research team led by investigators from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute has identified a promising new approach to the treatment of acute myeloid leukemia (AML). In their report published online in Cell, the investigators identify a crucial dysfunction in blood cell development that underlies AML and show that inhibiting the action of a specific enzyme prompts the differentiation of leukemic cells, reducing their number and decreasing their ability to propagate the cancer.
“AML is a devastating form of cancer; the five-year survival rate is only 30 percent, and it is even worse for the older patients who have a higher risk of developing the disease,” says David Scadden, MD, director of the MGH Center for Regenerative Medicine (MGH-CRM), co-director of the Harvard Stem Cell Institute (HSCI), and senior author of the Cell paper. “New therapies for AML are extremely limited - we are still using the protocols developed back in the 1970s - so we desperately need to find new treatments.”
In AML, the normal process by which myeloid stem cells differentiate into a specific group of mature white blood cells is halted, leading to the proliferation of immature, abnormal cells that crowd out and suppress the development of normal blood cells. A wide range of genetic changes occurs in AML, but the authors proposed that the effects on differentiation had to funnel through a few shared molecular events. Using a method created by lead author David Sykes, MD, PhD, of the MGH-CRM and HSCI, the team discovered that a single dysfunctional point in the pathway common to most forms of AML could be a treatment target.

Fatty acids in the breast may be useful indicators of cancer in postmenopausal women, according to a new study published online in the journal Radiology. The results may help researchers determine the underlying mechanisms behind breast cancer development in some patients.
The role of fat in breast cancer development and growth has been studied extensively using body mass index (BMI) and dietary fat intake.
“BMI is an important risk factor for breast cancer development,” said Sungheon G. Kim, Ph.D., from the NYU Langone Medical Center. “While increased BMI may provide a protective effect for premenopausal women, postmenopausal women have an increased risk of developing breast cancer with increasing BMI.”

A study led by Loyola Medicine researchers may help reassure patients who worry the breast cancer drug tamoxifen could increase their risk of uterine cancer.
The multi-center study was presented during the 2016 annual meeting of the American Society of Clinical Oncology at McCormick Place in Chicago. First author of the study is Kathy S. Albain, MD, FACP, FASCO. The study’s co-principal investigator is Ronald K. Potkul, MD, FACS, FACOG. Dr. Albain is a professor in the department of medicine, division of hematology/oncology, and Dr. Potkul is chair of the department of obstetrics and oncology of Loyola University Chicago Stritch School of Medicine.
The study enrolled 296 eligible postmenopausal breast patients with a type of early-stage breast cancer called estrogen receptor-positive. Patients were randomly assigned to take tamoxifen alone or tamoxifen plus the hormone progestin. They were followed and assessed at years two and five. Researchers predicted that taking progestin would decrease the risk of abnormalities that can develop into uterine cancer. Such abnormalities occur in the endometrium (inner lining of the uterus).

Two linked papers in The BMJ this week shed new light on the relation of alcohol and diet with breast cancer and heart disease.
The first study reports that high fruit consumption during adolescence may be associated with lower breast cancer risk, while the second study finds that increasing alcohol intake in later life is associated with an increased risk of breast cancer.
Fruit and vegetables are thought to protect against breast cancer, but the evidence is conflicting. Most studies have assessed intakes during midlife and later, which may be after the period when breast tissue is most vulnerable to carcinogenic influences.

Conventional chemotherapy generally fails to eradicate aggressive breast cancers due to the early distant metastasis that can occur in these diseases. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype which has no targeted treatment. It has recently been discovered that the oncogene MYC is elevated in TNBC, opening up promising opportunities for the development of new targeted therapeutic strategies that will allow selective killing of MYC-overexpressing TNBC cells.
With support from a Department of Defense Breast Cancer Era of Hope Scholar Award, Dr. Andrei Goga has taken a multi-faceted approach to identifying new therapeutic targets in MYC-driven TNBCs. In the first part of the study, Dr. Goga’s team used a fluorescence activated cell sorting (FACS) assay to isolate disseminated tumor cells (DTCs) from patient-derived xenograft models (PDX) of breast cancer. DTCs are the cancer cells that no longer reside with a primary tumor but occupy a peripheral tissue and may develop metastatic tumors. FACS was used to sort cells based on the expression of human cell marker CD298, allowing for detection of early DTCs as well as DTCs from late stage metastatic tumor-burdened tissues. Gene signatures of isolated cells could then be determined by qPCR.
The Goga team found that metastatic cells from low tumor-burdened tissues had enhanced stem cell-like gene signatures, while those from high-burdened tissues displayed signatures closer to that of the primary tumor.

Men with low levels of the male sex hormone testosterone need not fear that testosterone replacement therapy will increase their risk of prostate cancer.
This is the finding of an analysis of more than a quarter-million medical records of mostly white men in Sweden, research led by investigators at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center. The international team of study authors will present these results on May 9 at the annual meeting of the American Urological Association in San Diego, Calif.
In the study, researchers found that, as a group, men prescribed testosterone for longer than a year had no overall increase in risk of prostate cancer and, in fact, had their risk of aggressive disease reduced by 50 percent.

Being on the lookout for certain features of polyps may help physicians keep a closer eye on patients at risk for colorectal cancer.
Starting at age 50, or earlier with certain risk factors, patients are advised to be screened for colon cancer at regular intervals. Colonoscopy is an effective screening test because it allows doctors to find and view individual polyps (growths), and to remove them before they become cancerous.
Adenomas are polyps (small growths in the lining of the colon) that can vary in their size and shape, but are potentially precursors to colon cancer. Removal of these polyps reduces the risk of colon cancer. Flat adenomas are precancerous polyps that do not have a typical polyp- like appearance during endoscopy.

Everyone knows smartphones can be used as calendars, calculators, radios and cameras. But, did you know they can also be used as microscopes that have the potential to save lives?
They are called smartphone microscopes and dermatologists at The University of Texas Health Science Center at Houston (UTHealth) think these devices could improve the detection of skin cancer in developing countries.
“Doctors in some remote areas don’t have access to the high-powered microscopes we use to evaluate skin samples,” said Richard Jahan-Tigh, M.D., assistant professor of dermatology at John P. and Kathrine G. McGovern Medical School at UTHealth. “Doctors there could conceivable use their smartphones to photograph growths and forward them for examination.”

Consumption of broccoli has increased in the United States over the last few decades as scientists have reported that eating the vegetable three to five times per week can lower the risk of many types of cancer including breast, prostate, and colon cancers.
A new study from the University of Illinois reports that including broccoli in the diet may also protect against liver cancer, as well as aid in countering the development of fatty liver or nonalcoholic fatty liver disease (NAFLD) which can cause malfunction of the liver and lead to hepatocellular carcinoma (HCC), a liver cancer with a high mortality rate.
“The normal story about broccoli and health is that it can protect against a number of different cancers. But nobody had looked at liver cancer,” says Elizabeth Jeffery, a U of I emeritus professor of nutrition. “We decided that liver cancer needed to be studied particularly because of the obesity epidemic in the U.S. It is already in the literature that obesity enhances the risk for liver cancer and this is particularly true for men. They have almost a 5-fold greater risk for liver cancer if they are obese.”

Male breast cancer (MBC) is a very rare tumor type, occurring in just 1% of all breast cancer cases, and the underlying genetic causes and treatment of MBC is not well understood. In a paper published in the March issue of Cold Spring Harbor Molecular Case Studies, researchers from Italy and the U.S. describe novel genetic variants found in a hormone receptor positive (HR+) MBC patient, that are distinct from previously identified genetic variants found in ten MBC cases.
The authors present the treatment history of a HR+ male breast cancer patient. His disease stabilized from targeting of the PI3K/mTOR pathway using the PI3K/mTOR inhibitor BEZ235 in combination with everolimus as 3rd line treatment for his metastatic ductal carcinoma and experienced a prolonged stable disease. After 18 months he subsequently became resistant to the treatment and his disease progressed. The authors then investigated why the patient benefited and subsequently developed resistance to this combination treatment using genomic and immunohistochemical analysis.
Whole-exome sequencing was performed on pre-treatment and post-progression samples of the MBC patient, as compared to a whole blood normal control. The researchers found that a region of Chromosome 12p was deleted in the resistant tumor and that HR protein expression was increased in the resistant tumor.

Researchers at Princess Margaret Cancer Centre have confirmed in a screening effectiveness study that early screening with MRIs can reduce breast cancer mortality for female survivors of childhood Hodgkin’s lymphoma (HL) who received chest radiation.
The findings published today in the Journal of the National Cancer Institute (doi:10.1093/jnci/djw010), build on previous clinical work that demonstrated MRI detects breast cancer at early stages in young survivors who are not old enough to start standard breast cancer screening, says principal investigator Dr. David Hodgson, a radiation oncologist at the Princess Margaret Cancer Centre, University Health Network. Dr. Hodgson is also a Professor in the Department of Radiation Oncology, Faculty of Medicine at the University of Toronto.
“If you are a young woman who was treated with radiation therapy to your chest as a teenager or child for HL, or for that matter chest radiation therapy for any reason, you should be having a conversation with your family doctor or your oncologist about whether to start breast cancer screening earlier than most women would,” says Dr. Hodgson.